1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 3: Design, synthesis and SAR of orally bioavailable benzamidine-P4 inhibitors

…, ST Edwards, A Hutchaleelaha, SJ Hollennbach…

Index: Jia, Zhaozhong J.; Wu, Yanhong; Huang, Wenrong; Zhang, Penglie; Song, Yonghong; Woolfrey, John; Sinha, Uma; Arfsten, Ann E.; Edwards, Susan T.; Hutchaleelaha, Athiwat; Hollennbach, Stanley J.; Lambing, Joseph L.; Scarborough, Robert M.; Zhu, Bing-Yan Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 5 p. 1229 - 1234

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Citation Number: 55

Abstract

Using N, N-dialkylated benzamidines as the novel P4 motifs, we have designed and synthesized a class of 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides as highly potent and selective fXa inhibitors with significantly improved hydrophilicity and in vitro anticoagulant activity. These benzamidine-P4 fXa inhibitors have displayed excellent oral bioavailability and long half-life.